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08 September 2026, Volume 30 Issue 25 Previous Issue    Next Issue

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10-Hydroxy-2-decenoic acid facilitates osteogenic differentiation via the enhancement of autophagy and antioxidant capacity Hu Jie, He Hui, Ma Fengyu, Shen Xiaotian, Yuan Zhangqin, Liang Ting, Han Fengxuan 2026, 30 (25):  6433-6445.  doi: 10.12307/2026.455 Abstract ( 19 )   PDF (10067KB) ( 17 )   Save BACKGROUND: 10-Hydroxy-2-decenoic acid (10-HDA) exhibits potent anti-inflammatory, antioxidant, and immunomodulatory effects, but its role in regulating bone metabolism remains unclear. OBJECTIVE: To investigate the regulatory effects and underlying mechanisms of 10-HDA on bone remodeling. METHODS: (1) Bone marrow-derived mesenchymal stem cells were isolated from rats and treated with different concentrations of 10-HDA (0, 0.5, 1, 2, and 4 mmol/L). Cytoskeletal staining was used to assess cell morphology, while live/dead staining and the cell counting kit-8 assay were employed to evaluate cell viability and proliferation. (2) Bone marrow-derived mesenchymal stem cells were isolated from rats and treated with different concentrations of 10-HDA (0, 0.5, 1, and 2 mmol/L). After osteogenic induction, alkaline phosphatase staining and alizarin red staining were conducted to assess osteogenic differentiation. The expression of osteogenesis-related proteins was analyzed by western blot and immunofluorescence staining. (3) Mouse bone marrow mononuclear cells were induced to differentiate into macrophages by adding osteoclast-inducing differentiation medium containing different concentrations of 10-HDA (0, 0.5, 1, and  2 mmol/L). Tartrate-resistant acid phosphatase staining and F-actin staining were used to evaluate osteoclast formation. (4) Rat bone marrow mesenchymal stem cells were starved for 6 hours before conventional culture and grouped as follows: control group (no intervention), 10-HDA group, 10-HDA + AS1842856 group, 10-HDA + EX-527 group. 10-Hydroxy-2-decenoic acid was administered at a concentration of 0.5 mmol/L. AS1842856 was a forkhead box transcription factor O1 inhibitor, and EX-527 was a silent information regulator 1 inhibitor. Furthermore, activation of the silent information regulator 1/forkhead box transcription factor O1 signaling pathway and expression of autophagy- and antioxidant-related proteins were assessed by western blot and immunofluorescence. (5) Rat bone marrow mesenchymal stem cells were cultured in five groups: control group, H₂O₂ group, and H₂O₂ + 10-HDA group. The intervention concentration of 10-HDA was 0.5 mmol/L. Corresponding drug interventions were administered 24 hours after H₂O₂ exposure. After osteogenic induction, alkaline phosphatase staining and alizarin red staining were conducted. (6) Rat bone marrow mesenchymal stem cells were cultured in five groups: control group, H₂O₂ group, H₂O₂+10-HDA group, H₂O₂+10-HDA+AS1842856 group, and H₂O₂+10-HDA+EX-527 group. The intervention concentration of 10-HDA was 0.5 mmol/L. Corresponding drug interventions were administered 24 hours after H₂O₂ exposure. Western blot analysis was performed to detect the expression of silent information regulator 1/forkhead box transcription factor O1 signaling pathway and antioxidant-related proteins. TUNEL staining and β-galactosidase staining were performed to evaluate apoptosis and senescence.  RESULTS AND CONCLUSION: (1) At the concentration of 0.5, 1, and 2 mmol/L, 10-HDA promoted the proliferation of bone marrow-derived mesenchymal stem cells. Therefore, these three intervention concentrations were selected for subsequent experiments. (2) 10-HDA (0.5 mmol/L) significantly enhanced the osteogenic differentiation and mineralization of bone marrow-derived mesenchymal stem cells and increased the expression of osteogenesis-related proteins, as evidenced by alkaline phosphatase staining, alizarin red staining, western blot and immunofluorescence staining. (3) Tartrate-resistant acid phosphatase staining and F-actin staining revealed that 0.5 mmol/L 10-HDA significantly inhibited osteoclast formation. (4) Western blot and immunofluorescence staining revealed that 10-HDA activated the silent information regulator 1/forkhead box transcription factor O1 signaling pathway to promote deacetylation and nuclear translocation of forkhead box transcription factor O1, thereby upregulating autophagy-related proteins and antioxidant enzymes. (5) Alkaline phosphatase and alizarin red staining revealed that 10-HDA promotes osteogenic differentiation and mineralization in rat bone marrow-derived mesenchymal stem cells under oxidative stress conditions. (6) Western blot analysis revealed that under oxidative stress conditions, 10-HDA enhanced the antioxidant capacity of rat bone marrow mesenchymal stem cells by activating the silent information regulator 1/forkhead box transcription factor O1 signaling pathway. TUNEL and β-galactosidase staining revealed that under oxidative stress conditions, 10-HDA reduced apoptosis and senescence in rat bone marrow mesenchymal stem cells by activating the silent information regulator 1/forkhead box transcription factor O1 signaling pathway. To conclude, 10-HDA enhances autophagy and antioxidant capacity by regulating the silent information regulator 1/forkhead box transcription factor O1 signaling pathway, thereby promoting osteogenic differentiation. Key words: osteoporosis; bone marrow-derived mesenchymal stem cells; 10-hydroxy-2-decenoic acid; osteogenic differentiation; osteoclasts; silent information regulator 1; autophagy; antioxidant Figures and Tables | References | Related Articles | Metrics

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Transcriptomic analysis of expression and function of differential genes in traditional Chinese medicine syndromes of postmenopausal osteoporosis He Yanyan, Ge Jirong, Li Shengqiang, Chen Xuan, Huang Jingwen, Huang Xiaobin, Xue Lipeng 2026, 30 (25):  6446-6454.  doi: 10.12307/2026.479 Abstract ( 20 )   PDF (5653KB) ( 14 )   Save BACKGROUND: Kidney yin-yang deficiency syndrome in postmenopausal osteoporosis holds particular clinical significance due to its complex characteristics. Analysis of its differential genes is crucial for uncovering its molecular mechanisms. OBJECTIVE: To identify differential genes and signaling pathways associated with kidney yin-yang deficiency syndrome by comparing differential gene expression profiles across different kidney deficiency syndromes in postmenopausal osteoporosis, thereby revealing its molecular biological characteristics and providing an objective basis for traditional Chinese medicine syndrome differentiation. METHODS: Eighteen postmenopausal osteoporosis patients with kidney deficiency syndromes (six cases each of kidney yang deficiency, kidney yin deficiency, and kidney yin-yang deficiency) were enrolled, and an additional six healthy postmenopausal women were included as a healthy control group. Transcriptome sequencing was used to screen for differential genes, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The expression levels of four target genes (HSP90AB4P, CTU1, ST6GALNAC2, and PTGS2) were validated by qRT-PCR. RESULTS AND CONCLUSION: (1) Compared with the healthy control group, the kidney yin-yang deficiency syndrome group, the kidney yin deficiency group, and the kidney yang deficiency group yielded 235, 247, and 4 557 differentially expressed genes, respectively. Intersection analysis of the three comparison groups identified 22 differential genes associated with the kidney yin-yang deficiency syndrome group (18 up-regulated and 4 down-regulated). (2) qRT-PCR showed that the up-regulation and down-regulation trends of the target genes were consistent with the transcriptome sequencing results. (3) Gene Ontology analysis showed that biological processes focused on energy metabolism (nicotinamide adenine dinucleotide synthesis and metabolism) and physiological homeostasis (thermogenesis and blood pressure regulation); molecular functions involved immune defense, metabolic regulation, inflammation and signal transduction, and ion channel regulation; and cellular components were associated with ribosomes, endoplasmic reticulum, nucleus, and transfer RNA modification. (4) Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified 60 pathways, including apoptotic cell clearance, nuclear factor κB, tumor necrosis factor, interleukin 17, vascular endothelial growth factor, forkhead box O signaling pathways, and metabolic pathways. Overall, these findings suggest that postmenopausal osteoporosis with kidney yin-yang deficiency syndrome is a comprehensive manifestation of multidimensional molecular network imbalance, associated with ribosomal synthesis disorders, non-coding RNA-mediated signal or transcriptional regulation, immune-inflammatory regulation, and metabolic transport. Figures and Tables | References | Related Articles | Metrics

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Transcriptome sequencing analysis of tibial transverse transport in a rabbit model of diabetic foot ulcers Li Haojie, Xie Tongliang, Li Rui, Sun Zuyan, Deng Jiang, Xu Lin, Huang Wenliang 2026, 30 (25):  6455-6462.  doi: 10.12307/2026.475 Abstract ( 27 )   PDF (9675KB) ( 10 )   Save BACKGROUND: Tibial transverse transport has emerged as a pivotal therapeutic approach for severe diabetic foot ulcers (Wagner grade III and above); however, its precise molecular regulatory mechanisms remain largely elusive. OBJECTIVE: To establish an animal model of tibial transverse transport for diabetic foot ulcer treatment and perform transcriptome sequencing, aimed at identify significantly differentially expressed miRNAs and key target genes, as well as construct the corresponding miRNA-mRNA regulatory network. METHODS: A diabetic foot ulcer wound model was established in rabbits and treated with tibial transverse transport. Peripheral blood samples were collected for miRNA-seq and mRNA-seq. Differentially expressed miRNAs and mRNAs were identified through bioinformatics analysis of sequencing data. Target genes of miRNAs were predicted using TargetScan and miRanda, and a miRNA-mRNA regulatory network was constructed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis were performed on the target genes in the network. Core target genes were subsequently screened using the Maximal Clique Centrality and Degree algorithms. RESULTS AND CONCLUSION: A total of 9 miRNAs and 2 667 mRNAs with significant differential expression were identified. Based on the differential analysis results and miRNA target gene predictions, a miRNA-mRNA regulatory network containing 7 miRNAs and 79 target genes was constructed. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these target genes were primarily involved in the metabolic pathway, protein processing in endoplasmic reticulum, FoxO signaling pathway, propanoate metabolism, N-glycan biosynthesis, and other signaling pathways. Protein-protein interaction analysis revealed the interaction between the expressed proteins of these target genes and identified BAG3, AKT3, PPP4C, SEC61A1, DNAJC3, USP7, DAD1, and SETD7 as the core target genes. This study identified a series of key miRNAs, target genes, and signaling pathways associated with the treatment of diabetic foot ulcers through transcriptome sequencing. These findings not only provide new candidate targets for treating diabetic foot ulcers but also open new avenues for further exploration of the therapeutic mechanisms of tibial transverse transport. Figures and Tables | References | Related Articles | Metrics

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Grape seed proanthocyanidin oligomers alleviate demyelination in cuprizone-fed mice Wang Qing, Yang Zhichao, Liu Jian, Liang Yajie, Tang Yibin, Guo Yu, Song Guobin, Ma Cungen 2026, 30 (25):  6463-6471.  doi: 10.12307/2026.433 Abstract ( 20 )   PDF (2267KB) ( 6 )   Save BACKGROUND: Recent studies on the pathogenesis of multiple sclerosis suggest that intervening in glial cells may play a key role in reducing relapses and delaying disability progression. Grape seed proanthocyanidin oligomers significantly inhibit demyelination in cuprizone-treated mice. OBJECTIVE: To explore the mechanism by which grape seed proanthocyanidin oligomers protect myelin sheaths through regulating astrocytes.  METHODS: (1) Animal experiment: Thirty mice were randomly divided by body mass into a normal group, a cuprizone group, and a cuprizone+oligomeric proanthocyanidins group. The latter two groups were fed a diet containing 0.2% cuprizone daily for 6 weeks to induce a demyelination model. Starting from the 5th week, mice in the normal and cuprizone groups received oral administration of ddH₂O₂, while mice in the cuprizone+oligomeric proanthocyanidins group received oral administration of grape seed proanthocyanidin oligomers [50 mg/(kg·d)] once daily for 2 consecutive weeks. Behavioral changes in mice were observed, pathological changes of myelin sheaths using LFB and oil red O staining, inflammatory factor levels in the brain were measured using ELISA, and expression of relevant proteins in the brain was detected using immunofluorescence staining. (2) Cell experiment: Grape seed proanthocyanidin oligomers (30 μg/mL) were used to intervene in an astrocyte inflammation model in vitro induced by tumor necrosis factor-α, interleukin-1α, and C1q. Conditioned medium was collected and used to culture oligodendrocytes. Cells were then divided into normal, model, and model+oligomeric proanthocyanidin groups. Oligodendrocyte injury and cell viability were assessed using L-lactate dehydrogenase and cell counting kit-8 assays, while western blot assay was used to detect apoptosis-related protein expression. RESULTS AND CONCLUSION: (1) Grape seed proanthocyanidin oligomers significantly ameliorated myelin loss in cuprizone-treated mice by suppressing pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-1α, and interleukin-17) and promoting the secretion of anti-inflammatory transforming growth factor-β. This was accompanied by the proliferation of astrocytes, a significant reduction in C3d (a marker of proinflammatory astrocytes), and suppression of JNK (a signaling molecule associated with astrocyte polarization) phosphorylation in the corpus callosum. (2) Compared with the model group, conditioned medium treated with grape seed proanthocyanidin oligomers significantly reduced apoptosis in oligodendrocytes induced by inflammatory astrocytes, promoted Bcl-2 expression, and inhibited Bax and Caspase-3 expression in oligodendrocytes. To conclude, grape seed proanthocyanidin oligomers protect against cuprizone-induced demyelination by inhibiting JNK phosphorylation in astrocytes, thereby reducing pro-inflammatory A1 polarization and subsequently inhibiting apoptosis in oligodendrocytes induced by inflammatory astrocytes. Figures and Tables | References | Related Articles | Metrics

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Integrated proteomics and transcriptomics analysis of the mechanism of Buyang Huanwu Tang in protecting the acute spinal cord injury rat model Wang Ziqi, Bu Xianzhong, Guo Xiaohui, Li Hanxi, Qian Yuhao, Wang Yixin, Bu Baoxian 2026, 30 (25):  6472-6488.  doi: 10.12307/2026.235 Abstract ( 19 )   PDF (28055KB) ( 9 )   Save BACKGROUND: Research indicates that Buyang Huanwu Tang has positive therapeutic effects on the spinal cord injury symptoms and spinal cord function recovery, although its therapeutic mechanisms remain unclear. Spinal cord tissue contains numerous proteins and peptides that may serve as disease biomarkers. OBJECTIVE: To investigate the protective mechanism of Buyang Huanwu Tang in an acute spinal cord injury rat model by regulating proteomic- and transcriptomic-related pathways. METHODS: Thirty-six Sprague-Dawley rats were randomly divided into control, model, and Buyang Huanwu Tang groups. An acute spinal cord injury model was established in the latter two groups using Allen's modified method. Motor function recovery was evaluated using the Basso-Beattie-Bresnahan score. Histopathology was examined via Nissl staining. Differentially expressed proteins and genes were screened using isobaric tags for relative and absolute quantitation proteomics and RNA sequencing transcriptomics. Gene Ontology enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and protein-protein interaction network constructed with Search Tool for the Retrieval of Interacting Genes/Proteins interaction network database were employed to identify key pathways, and core targets were validated through Western blot, immunohistochemistry, and real-time polymerase chain reaction. RESULTS AND CONCLUSION: (1) Motor score: Compared with the blank group, rats in the model group exhibited significantly lower Basso-Beattie-Bresnahan motor scores in the hindlimbs (P < 0.001) and markedly smaller inclined angles in the inclined plane test (P < 0.001). Compared with the model group, rats in the Buyang Huanwu Tang group showed higher Basso-Beattie-Bresnahan motor scores in the hindlimbs (P < 0.05). and significantly larger incline angle in the inclined plane test (P < 0.001). Pathological morphological observations: The control group exhibited relatively normal neuronal morphology with intact cellular structures, normal intercellular spaces, and clearly visible nucleoli and nuclear membranes. The model group showed severe cellular necrosis, disorganized structures, condensed nuclei, and loss of most nucleoli and nuclear membranes, along with extensive tissue cavities and inflammatory cell infiltration. The Buyang Huanwu Tang group exhibited irregularly shaped but relatively intact neuronal cells with mild swelling, reduced tissue cavities, and decreased cellular necrosis. (2) Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes signaling pathway annotation results revealed that differentially expressed proteins primarily participated in the regulation of acute phase response, protein activation cascade, and acute inflammatory response, and the molecular function of platelet alpha granule, blood microparticle, vacuolar lumen, serine propeptidase inhibitor activity, etc, and participated in the map04142 lysosome, map04612 antigen processing and presentation, map03013 nucleocytoplasmic transport, map04964 proximal tubule bicarbonate reclamation, map04610 complement and coagulation cascades, map00511 other glycan degradation, map03040 spliceosome, map03410 base excision repair, map00531 glycosaminoglycan degradation, and the coronavirus disease-COVID-19 pathways. The protein-protein interaction analysis showed 20 hub differentially expressed proteins, including FGG, FN1, FGB, HSP90B1, and CASP3, and 20 core differentially expressed genes, including FGG, FN1, FGB, CXCL1, and CXCL13, were identified. (3) Western blot analysis demonstrated that Buyang Huanwu Tang inhibits the protein expression of myeloid differentiation primary response protein 88 and phosphor-I-kappa-B-alpha in spinal cord tissue. Immunohistochemical analysis demonstrated that Buyang Huanwu Tang suppresses BAX and Caspase-3 protein expression while promoting BCL-2 protein expression in spinal cord tissue, thereby inhibiting apoptosis. Real-time polymerase chain reaction results indicated that Buyang Huanwu Tang suppresses the mRNA expression of myeloid differentiation primary response protein 88 and C-X-C motif chemokine ligand 1 in spinal cord tissue. Taken together, these findings suggest that Buyang Huanwu Tang may protect spinal cord tissue by reducing the inflammatory response through the inhibition of the Toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor-kappa B pathway, and by preventing apoptosis via regulation of the BAX/BCL-2 balance and suppression of Caspase-3 expression.   Figures and Tables | References | Related Articles | Metrics

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Efficiency of anterior tooth intrusion in deep overbite cases with clear aligners: analysis via the indirect model superimposition method Wang Shiyu, Huang Yangyang, Liu Hao, Xu Jiabin, Wang Penglai, Yang Li 2026, 30 (25):  6489-6495.  doi: 10.12307/2026.385 Abstract ( 14 )   PDF (5757KB) ( 8 )   Save BACKGROUND: Anterior tooth intrusion is commonly used in the deep overbite cases with clear aligners. However, the intrusion efficiency varies significantly among different cases. OBJECTIVE: To analyze and compare the intrusion efficiency of the anterior teeth with clear aligners by the indirect model superimposition method based on the occlusal records.  METHODS: Forty-three patients with anterior deep overbite were selected as the subjects of this study and divided into the non-extraction and extraction groups. The non-extraction group was then divided into the alignment and maxillary molar distalization subgroups. The extraction group was subdivided into the first premolar extraction and second premolar extraction subgroups. In the Geomagic 2014 software, the occlusal plane inclinations of the pre- and post-treatment models were calibrated based on the angle between the Frankfort plane and occlusal plane. The maxillary and mandibular models were superimposed by the maxillary palatine folds and occlusal records. Based on the Frankfort plane, the measurement coordinate system was established to measure the actual intrusion amount. The relative intrusion amount in the ClinCheck protocol was recorded as the designed intrusion amount.   RESULTS AND CONCLUSION: (1) The actual intrusion amount of the anterior teeth was significantly less than the designed intrusion amount in the non-extraction and extraction groups (P < 0.01). Overcorrection should be designed in the anterior intrusion using clear aligners. (2) The intrusion efficiency in the non-extraction group (50.69%) was significantly higher than that in the extraction group (39.73%) (P < 0.01). More overcorrection was required in the extraction cases. (3) The intrusion efficiency of the mandibular anterior teeth was significantly higher than that of the maxillary anterior teeth (P < 0.01). More overcorrection was required in the intrusion of maxillary anterior teeth. (4) There was no significant difference in the intrusion efficiency between the alignment subgroup and maxillary molar distalization subgroup (P > 0.05). (5) The intrusion efficiency of the second premolar extraction subgroup was significantly higher than that of the first premolar extraction subgroup (P < 0.01). Extracting the second premolars was more beneficial for the vertical control of the anterior teeth than extracting the first premolars. (6) There was a linear relationship between the designed and actual intrusion amount between the groups. The regression equation could provide reference for the clinicians to design personalized overcorrection amount based on different teeth and treatment protocols. Figures and Tables | References | Related Articles | Metrics

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Magnetic calcium-regulated mitochondrial sensitivity in adolescents: assessment of skeletal muscle function and body composition Li Zhongshan, Li Wenhao, Du Xinran, Yang Tieli, Bai Shi 2026, 30 (25):  6496-6505.  doi: 10.12307/2026.279 Abstract ( 13 )   PDF (1832KB) ( 6 )   Save BACKGROUND: Magnetic mitochondrial calcium regulation technology, as a non-invasive method for promoting skeletal muscle function, has been effectively demonstrated in improving muscle function and enhancing metabolic sensitivity. Existing studies have shown that this technology has significant physiological promoting effects on adults, the elderly, and postoperative rehabilitation groups. However, its intervention effect on skeletal muscle function and body composition in 12-13-year-old adolescents remains unclear. OBJECTIVE: To explore the sensitivity of skeletal muscle function and body composition in 12-13-year-old adolescents to magnetic stimulation by assessing their skeletal muscle function and body composition. METHODS: Thirty-four junior high school students in Grade 7 from Liaoning Province Experimental School were recruited and randomly divided into a control group and a trial group. The control group maintained their daily school activities without any specific physical training plan. In addition, the trial group received low-frequency pulsed magnetic field intervention twice a week (stimulation duration 10 minutes, magnetic field strength 1.5 mT, frequency 3 300 Hz, intervention once every 72 hours) for four consecutive weeks. Changes in maximum strength, explosive power, endurance, and body composition-related indicators at the intervention sites were observed before the start of the trial (pre-test) and after the end of the trial (post-test).  RESULTS AND CONCLUSION: (1) After 8 sessions of low-frequency pulsed magnetic field stimulation over 4 weeks, the subjects showed significant improvements in explosive power, aerobic endurance, isometric endurance, and body composition-related indicators, indicating that 12-13-year-old adolescents had good sensitivity to magnetic calcium regulation stimulation for the aforementioned skeletal muscle function and body composition. (2) The effect on maximum strength improvement was not significant, and their muscle magnetic sensitivity was lower than that of adults, but they showed some advantages in maintaining maximum strength under prolonged sedentary conditions. These results suggest that magnetic mitochondrial calcium regulation technology, as a novel passive and non-invasive skeletal muscle function enhancement technique, could be explored as a novel intervention to improve the physical health of adolescents. Figures and Tables | References | Related Articles | Metrics

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Highly sensitive indicators of neck muscle fatigue derived from multimodal electrophysiological and metabolic coupling analysis Liu Yakun, Lu Guangqi, Liang Long, Li Jing, Sun Xinyue, Liu Guangwei, Zhou Shuaiqi, Mao Hanze, Ma Mingming, Hu Jiaming, Zhu Liguo, Zhuang Minghui, Yu Jie 2026, 30 (25):  6506-6511.  doi: 10.12307/2026.499 Abstract ( 19 )   PDF (1402KB) ( 7 )   Save BACKGROUND: Prolonged forward head posture induces neck muscle fatigue, a significant contributing factor to cervical spondylosis. Current unimodal monitoring approaches are inadequate to capture the dynamic coupling among muscle activation, metabolic activity, and motor control. OBJECTIVE: To systematically evaluate the temporal characteristics of neck muscle fatigue using multimodal monitoring technology, thereby providing a theoretical foundation for early detection and intervention of cervical fatigue. METHODS: Twenty healthy participants were recruited. Surface electromyography, near-infrared spectroscopy, and three-dimensional motion capture technology were synchronized to record electrophysiological signals, oxygenated hemoglobin concentration, and cervical kinematics during a sustained 45° static forward flexion task until subjective fatigue was reached (Borg CR-10 score ≥ 4). Temporal changes in root mean square amplitude, mean power frequency, muscle oxygen saturation, and normalized forward head angle were analyzed across fatigue stages segmented into 10% intervals of total endurance time. RESULTS AND CONCLUSION: (1) The root mean square amplitude increased significantly (P < 0.001), while mean power frequency and muscle oxygen saturation decreased significantly (P < 0.001) throughout the task, with the reduction in muscle oxygen saturation commencing from the 40% fatigue stage. (2) Linear regression analyses revealed a stronger association between mean power frequency and muscle oxygen saturation (upper trapezius: R² = 0.58; middle trapezius: R² = 0.61), indicating that metabolic alterations preceded detectable electrophysiological changes. (3) The upper trapezius demonstrated earlier fatigue onset compared with the middle trapezius (P < 0.05). These findings suggest that multimodal integration of combined mean power frequency and muscle oxygen saturation monitoring serves as a highly sensitive strategy for early fatigue detection. Figures and Tables | References | Related Articles | Metrics

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Exploring the characteristics of neck muscle strength and activation in patients with cervical spondylotic radiculopathy using motion capture-Opensim digital simulation technology  Liu Qiuli, Liang Yuanyao, Han Bin, Li Zhifei, Zhang Zhanming, Wei Haokai, Zuo Kuangshi, Liu Jun 2026, 30 (25):  6512-6521.  doi: 10.12307/2026.472 Abstract ( 15 )   PDF (3014KB) ( 5 )   Save BACKGROUND: Modern research suggests that the “muscle-bone imbalance” in cervical spondylotic radiculopathy is associated with changes in the performance of cervical muscles due to biomechanical alterations of the head and neck. However, most studies have focused on static analysis of the cervical spine, lacking dynamic quantitative data on neck muscle strength and activation. OBJECTIVE: To investigate the differences in muscle strength and muscle activation during cervical spine movement between patients with cervical spondylotic radiculopathy and healthy individuals from a biomechanical perspective. METHODS: From October 1, 2023 to March 1, 2024, 10 volunteers were recruited from the orthopedic outpatient clinic, inpatient ward, and health check-up center of the First Affiliated Hospital of Guangxi University of Chinese Medicine. These included five patients with cervical spondylotic radiculopathy (cervical spondylotic radiculopathy group) and five healthy individuals (healthy control group). Inertial motion capture sensors were used to collect movement data of the neck in six degrees of freedom: cervical flexion, cervical extension, left lateralization, right lateralization, left rotation, and right rotation. Data were measured three times per participant, yielding 18 sets of data. Based on muscle parameters obtained from magnetic resonance imaging scans, OpenSim head and neck musculoskeletal models were established for patients and healthy individuals separately. After preprocessing, the collected cervical motion data were imported into the OpenSim simulation models to calculate and compare neck muscle strength and muscle activation between the two groups. RESULTS AND CONCLUSION: The healthy control group showed orderly synergistic activation of muscle groups, while the cervical spondylotic radiculopathy group exhibited disordered synergistic activation patterns, characterized by insufficient activation of affected-side muscles, excessive compensation on the unaffected side, and significantly reduced synergy of core muscles including the sternocleidomastoid, middle and upper trapezius, and longus colli. Muscle strength in the cervical spondylotic radiculopathy group was lower than that in the healthy control group (P < 0.05) as follows: during cervical extension (sternocleidomastoid, middle trapezius, longus capitis, upper trapezius); during cervical flexion (sternocleidomastoid, longus capitis, longus colli, levator scapulae, multifidus, splenius cervicis, splenius capitis, middle/upper trapezius); during left lateralization (sternocleidomastoid, longus capitis, longus colli, scalenus, levator scapulae, multifidus, splenius cervicis, splenius capitis, middle/upper trapezius); during right lateralization (longus colli, upper trapezius); during left rotation (levator scapulae); and during right rotation (longus colli). Overall, these findings indicate that patients with cervical spondylotic radiculopathy exhibit cervical muscle synergy imbalance during all cervical movements. This imbalance is characterized by degeneration of affected-side muscles and nerves with reduced muscle strength and coordination, while unaffected-side muscles and nerves overcompensate for the functional deficiency of the affected side. Among the muscle groups involved in cervical motion, degeneration of the sternocleidomastoid and the middle/upper trapezius is most significant, which is an important feature of cervical spondylotic radiculopathy. Figures and Tables | References | Related Articles | Metrics

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Establishment and validation of a Sprague-Dawley rat model of aging-related knee osteoarthritis Wu Zugui, Zhu Yue, Li Jiao, Yuan Rong, Wu Zhiwei, Li Junyi, Li Congcong, Shen Zhen, Guo Ying 2026, 30 (25):  6522-6532.  doi: 10.12307/2026.292 Abstract ( 22 )   PDF (5225KB) ( 7 )   Save BACKGROUND: Knee osteoarthritis is an age-related disease, and aging is closely related to its occurrence and development. Chondrocyte senescence plays a crucial role in the pathological progression of knee osteoarthritis.  OBJECTIVE: To establish a stable induced knee osteoarthritis model in SD rats.  METHODS: (1) Animal experiment: Forty Sprague-Dawley rats were randomly divided into four groups: a blank control group (n=10) without modeling; a D-galactose group (n=10) with intra-articular injection of D-galactose solution (once a week for two months), establishing age-related knee osteoarthritis models; an anterior cruciate ligament transection group (n=10) with anterior cruciate ligament transection, establishing knee osteoarthritis models; and a D-galactose + anterior cruciate ligament transection group (n=10) with intra-articular injection of D-galactose solution (once a week for two months) one week after anterior cruciate ligament transection, establishing age-related knee osteoarthritis models. Starting one week after modeling, all four groups of rats underwent running exercise for 30 minutes daily, every other day. At weeks 4 and 8 post-modeling, after behavioral testing (Lequesne MG score), tissue samples were collected for analysis of inflammatory factor levels in knee synovial fluid, pathological morphology of knee cartilage, transmission electron microscopy observation of knee cartilage, and immunohistochemical staining for type II collagen and aggregates in knee cartilage. (2) Cell experiments: At weeks 4 and 8 post-modeling, knee chondrocytes were isolated and extracted from each group of rats. Flow cytometry was used for cell cycle analysis, β-galactosidase staining, and γ-H2AX immunofluorescence staining. RESULTS AND CONCLUSION: (1) Animal experiments: At week 8 post-modeling, the Lequesne MG scores of rats in all three modeling groups were higher than those in the blank control group (P < 0.05). The Lequesne MG score of rats in the D-galactose + anterior cruciate ligament transection group was higher than that of the D-galactose group and the anterior cruciate ligament transection group (P < 0.05). At weeks 4 and 8 post-modeling, the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the synovial fluid of the knee joints in all three modeling groups were higher than those in the blank control group (P < 0.05). The levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the synovial fluid of the knee joints in the D-galactose + anterior cruciate ligament transection group were higher than those in the D-galactose group and the anterior cruciate ligament transection group (P < 0.05). Hematoxylin-eosin and safranin-fast green staining and transmission electron microscopy at weeks 4 and 8 post-modeling showed that cartilage damage and chondrocyte mitochondrial damage were more severe in the D-galactose + anterior cruciate ligament transection group than in the D-galactose group and the anterior cruciate ligament transection group. Immunohistochemical staining results at weeks 4 and 8 after modeling showed that the expression of type II collagen and proteoglycans in the knee cartilage of the blank control group was the highest, while the expression of type II collagen and proteoglycans in the knee cartilage of the D-galactose + anterior cruciate ligament transection group was lower than that of the D-galactose group + anterior cruciate ligament transection group. (2) Cell experiments: At weeks 4 and 8 after modeling, the proportion of chondrocytes in the G0/G1 phase of the D-galactose + anterior cruciate ligament transection group was higher than that of the other three groups (P < 0.05), while the proportion of cells in the S phase and G2/M phase was lower than that of the other three groups (P < 0.05). The positive rate of β-galactosidase staining and the intensity of H2AX immunofluorescence in chondrocytes of the D-galactose + anterior cruciate ligament transection group were both higher than those of the other three groups (P < 0.05). These results indicate that the D-galactose + anterior cruciate ligament transection method can establish an aging knee osteoarthritis model in SD rats, and this model can better simulate the pathological state of aging and degeneration in knee osteoarthritis.  Figures and Tables | References | Related Articles | Metrics

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Yanggan Roujin Decoction delays intervertebral disc degeneration: network pharmacological analysis and experimental validation in rat models Chen Chaoqi, Liu Fei, Song Chao, Shen Baoxin, Huang Wutao, Chen Feng, Yang Lei 2026, 30 (25):  6533-6543.  doi: 10.12307/2026.259 Abstract ( 13 )   PDF (11729KB) ( 12 )   Save BACKGROUND: The clinical efficacy of Yanggan Roujin Decoction in delaying intervertebral disc degeneration is significant; however, its underlying mechanism remains unclear. OBJECTIVE: To validate the potential mechanisms by which Yanggan Roujin Decoction delays intervertebral disc degeneration using network pharmacology techniques and animal experiments. METHODS: (1) The effective components of Yanggan Roujin Decoction and their action targets were screened using the Traditional Chinese Medicine Systems Platform and High-Throughput Experiment- and Reference-Guided Database of Traditional Chinese Medicine databases. Gene sets related to intervertebral disc degeneration were obtained from the Genecard, CTD, and DisGeNet databases. A protein-protein interaction network was constructed using the STRING database, and core targets were identified. The drug-component-target-disease network was constructed with Cytoscape 3.9.1 software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the core targets were performed using the Ouyi Biological Cloud platform to identify potential therapeutic mechanisms. (2) A rat model of intervertebral disc degeneration was established through percutaneous puncture of the annulus fibrosus, followed by intervention with varying doses of Yanggan Roujin Decoction and diclofenac sodium. Changes in intervertebral disc tissue structure before and after intervention were assessed through histopathological staining, and the expression levels of core targets and relevant pathways were analyzed using western blot assay and quantitative PCR. RESULTS AND CONCLUSION: (1) Network pharmacological analysis revealed that the active components of Yanggan Roujin Decoction consisted of 187 primary compounds, including beta-sitosterol, sitosterol, stigmasterol, quercetin, and kaempferol. The potential targets for treating intervertebral disc degeneration identified included 298 key proteins, primarily tumor protein 53, transcription factor c-Jun, interleukin-6, tumor necrosis factor-α, protein kinase B, and insulin. These targets were primarily involved in enzyme binding, nitric oxide synthase regulatory activity, and signaling pathways such as mitogen-activated protein kinase, hypoxia-inducible factor 1, tumor necrosis factor, interleukin-17. (2) Animal experiments demonstrated that Yanggan Roujin Decoction effectively alleviated the pathological changes in the intervertebral disc tissue structure caused by annulus fibrosus puncture. Compared with the normal group, the expression levels of tumor protein 53, transcription factor c-Jun, interleukin-6, and tumor necrosis factor-α were significantly elevated in the intervertebral disc tissues of rats in the model group (P < 0.01), whereas the expression levels of protein kinase B and insulin were significantly decreased (P < 0.01). The protein and mRNA levels of representative genes in the mitogen-activated protein kinase signaling pathway (38 and extracellular regulated protein kinases) and representative genes in the tumor necrosis factor pathway (interleukin-1β and tumor necrosis factor-α) were elevated, while the protein and mRNA levels of representative genes in the hypoxia-inducible factor-1α pathway (hypoxia-inducible factor-1α and vascular endothelial growth factor 1A) were reduced. After intervention with Yanggan Roujin Decoction at different doses, the protein and mRNA expression levels of tumor protein 53, transcription factor c-Jun, interleukin-6, tumor necrosis factor-α were significantly decreased (P < 0.01), while the protein and mRNA expression levels of protein kinase B and insulin were significantly increased (P < 0.01). Meanwhile, the protein and mRNA levels of representative genes in the mitogen-activated protein kinase signaling pathway (38 and extracellular regulated protein kinases) and representative genes in the tumor necrosis factor pathway (interleukin-1β and tumor necrosis factor-α) were reduced, while the protein and mRNA levels of representative genes in the hypoxia-inducible factor-1α pathway (hypoxia-inducible factor-1α and vascular endothelial growth factor 1A) were increased. After diclofenac sodium intervention, the expressions of interleukin 6 and tumor necrosis factor α at protein and mRNA levels were decreased (P < 0.01), and the protein and mRNA expressions of representative genes in the tumor necrosis factor signaling pathway (interleukin 1β and tumor necrosis factor α) decreased. However, there was no significant difference in the other indicators. To conclude, Yanggan Roujin Decoction effectively delays the progression of intervertebral disc degeneration, possibly through the regulation of tumor protein 53, transcription factor c-Jun, interleukin 6, tumor necrosis factor-α, protein kinase B, and insulin target genes, the inhibition of mitogen-activated protein kinase and tumor necrosis factor signaling pathways, and the activation of hypoxia-inducible factor 1 signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Combined proteomics and metabolomics analysis of pathological mechanisms in mouse models of coronary heart disease Liu Jinwei, Zhang Dan, Guo Hongli, Chen Huan, Li Jingjing, Cao Weiguo 2026, 30 (25):  6544-6553.  doi: 10.12307/2026.471 Abstract ( 11 )   PDF (2375KB) ( 5 )   Save BACKGROUND: The pathogenesis of coronary heart disease is complex. A single omics approach is limited in elucidating its biological pathways, whereas multi-omics integration helps reveal molecular interaction networks across different levels, addressing the limitations of single-omics methods. OBJECTIVE: To investigate the pathological mechanisms of coronary heart disease in a mouse model using proteomics and metabolomics. METHODS: Healthy SPF-grade 8-week-old male C57BL/6 mice were randomly divided into a sham operation group and a model group. The mouse model of coronary heart disease was established by ligation of the left anterior descending coronary artery, while the sham operation group underwent threading without ligation. At 28 days post-surgery, cardiac function was assessed by echocardiography, and myocardial infarct size was evaluated by TTC staining. Ultra-high-performance liquid chromatography-tandem mass spectrometry was employed to screen differentially expressed proteins and metabolites between groups for integrated omics analysis. RESULTS AND CONCLUSION: (1) Compared with the sham operation group, the model group exhibited significantly decreased cardiac function, with reduced left ventricular ejection fraction and fractional shortening (P < 0.05), and a significantly increased myocardial infarction area (P < 0.01). (2) Proteomics identified 420 differentially expressed proteins, including 282 upregulated (e.g., Serum amyloid A protein, protein kinase D) and 138 downregulated (e.g., Protein YIPF5, E3 ubiquitin-protein ligase). Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these proteins were mainly involved in ATP-dependent chromatin remodeling and the renin-angiotensin system. (3) Metabolomics identified 155 differential metabolites, with 56 upregulated (e.g., Thromboxane, Tromethamine) and 99 downregulated (e.g., N-Acetyl-D-Tryptophan, D-Xylulose 5-Phosphate). Kyoto Encyclopedia of Genes and Genomes analysis indicate the association between these metabolites and purine metabolism and glycerophospholipid metabolism pathways. (4) Integrated analysis revealed significant correlations between 26 differentially expressed proteins and 16 differential metabolites, involving proteins such as ATP1A3 and Hexokinase, and metabolites such as Cytochalasin B and Gluconasturtiin. To conclude, these findings suggest that the pathogenesis of coronary heart disease may be closely related to disturbances in energy metabolism networks, activation of inflammation-coagulation cascades, and imbalances in ion homeostasis regulation. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which astragalus-peach kernel alleviates renal fibrosis in chronic kidney disease rats Liu Jiayong, Yao Jingjing, Liu Shiyu, Tang Yi, Dong Jianing, Zhang Xin, Hou Lanwei, Kang Jianying, Zhao Yirui 2026, 30 (25):  6554-6565.  doi: 10.12307/2026.416 Abstract ( 16 )   PDF (4469KB) ( 6 )   Save BACKGROUND: Our previous studies have indicated that astragalus–peach kernel alleviates the progression of chronic kidney disease yet its precise mechanism remains to be elucidated. OBJECTIVE: To investigate the therapeutic effects and underlying mechanisms of astragalus-peach kernel in preventing renal fibrosis in chronic kidney disease rats. METHODS: (1) Gene expression profile chip datasets related to chronic kidney disease were retrieved and filtered via the Gene Expression Omnibus (GEO) database (this public gene expression database, established and maintained by the National Center for Biotechnology Information, which is primarily used for storing and sharing high-throughput genomic data. The database offers free download and analysis tools, serves as an open-access resource, and has obtained approval from relevant institutional review boards for its research). Disease-related core targets were screened via the GEO database combined with network pharmacology analyses. Key genes obtained were validated through molecular docking. (2) Forty Sprague-Dawley rats were randomly assigned into blank, model, dapagliflozin, and astragalus–peach kernel groups (n=10 each). A chronic kidney disease model was established by intragastric administration of a 2% adenine solution in the latter three groups. Starting the day after the induction of chronic kidney disease, the blank and model groups received saline via gastric lavage, while the dapagliflozin group received dapagliflozin via gastric lavage, and the astragalus–peach kernel group received astragalus–peach kernel (with a mass ratio of 1:1) via gastric lavage, once daily for 8 consecutive weeks. Following the final administration, serum creatinine and blood urea nitrogen levels in rat arterial blood were measured.  Renal tissue was examined via hematoxylin-eosin staining, Masson staining, and immunohistochemical staining for α-smooth muscle actin and type I collagen. RT-qPCR was used to detect mRNA expression of α-smooth muscle actin, type I collagen, transforming growth factor-β, and c-Myc in renal tissue. Western blot analysis was performed to detect protein expression levels of α-smooth muscle actin, type I collagen, transforming growth factor-β, c-Myc, Smad3, and p-Smad3 in renal tissue.  RESULTS AND CONCLUSION: (1) Through GEO-based network pharmacology analysis, nine active components of astragalus–peach kernel and seven core disease targets (c-Myc, RB1, CHUK, MAPK14, DPEP1, NR1I3, NQO2) were identified. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the Ras–MAPK–c-Myc pathway is associated with chronic kidney disease. Molecular docking suggested strong binding affinity between c-Myc and the core active compounds. (2) Compared with the blank group, the model group exhibited reduced glomerular number, structural abnormalities, pronounced inflammatory cell infiltration in renal tubules, extensive fibroblast proliferation in the renal tissue, and abnormal accumulation of collagen fibers in the renal interstitium. Serum creatinine and blood urea nitrogen levels, as well as the mRNA and protein levels of α-smooth muscle actin and type I collagen, were significantly elevated (P < 0.05). Compared with the model group, the astragalus–peach kernel group showed more intact renal histology, reduced inflammatory infiltration, and decreased fibroblast proliferation in the renal tissue. The astragalus–peach kernel treatment suppressed the elevations in serum creatinine and blood urea nitrogen levels and both mRNA and protein expression of α-smooth muscle actin and type I collagen (P < 0.05). Compared with the blank group, the model group showed significantly elevated mRNA and protein levels of c-Myc and transforming growth factor-β, as well as increased protein levels of Smad3 and p-Smad3 (P < 0.05). Compared with the model group, the astragalus–peach kernel treatment significantly downregulated mRNA and protein levels of c-Myc and transforming growth factor-β, as well as reduced protein levels of Smad3 and p-Smad3 (P < 0.05). These findings suggest that astragalus–peach kernel may slow chronic kidney disease progression in Sprague-Dawley rats, potentially through the modulation of the c-Myc/transforming growth factor-β/Smad3 signaling pathway.  Figures and Tables | References | Related Articles | Metrics

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Effects and mechanisms of glycemic variability on apoptosis in mouse hippocampal neuronal HT-22 cells Chen Di, Xu Mengling, Rao Binchan, Zhu Liying, Li Xing, Xu Yongjie, Pan Wei 2026, 30 (25):  6566-6574.  doi: 10.12307/2026.463 Abstract ( 18 )   PDF (6836KB) ( 7 )   Save BACKGROUND: Previous studies have confirmed that the “metabolic memory” effect induced by a sustained high-glucose environment can significantly exacerbate damage in mouse hippocampal neuronal cell lines HT-22 by regulating histone acetylase activity. OBJECTIVE: To investigate the effects of glycemic variability and sustained high glucose on apoptosis and the expression of histone deacetylase 4 and silent information regulator 1 in mouse hippocampal neuronal cell lines HT-22. METHODS: The 6th generation of HT-22 cells were adherent and divided into three groups for culture: a control group was cultured with 25 mmol/L glucose for 3 or 5 days; a high glucose group was cultured with 55 mmol/L glucose for 3 or 5 days; a glycemic variability group was cultured with 25 mmol/L glucose for 12 hours and then switched to 55 mmol/L glucose for 12 hours, with this fluctuation lasting for 3 or 5 days. After 3 days of culture, cell morphology was observed under an optical microscope. After 5 days of culture, cell apoptosis was detected by flow cytometry. After 3, 4, and 5 days of culture, cell viability was detected by cell counting kit-8 assay. After 3 and 5 days of culture, reactive oxygen species levels in cells were detected using a DCFH-DA fluorescent probe, histone deacetylase content in the cell supernatant was detected by ELISA, protein expression of Bax, Bcl-2, Caspase-3, Cleaved Caspase-3, silent information regulator 1, and histone deacetylase 4 in cells was detected by western blot, and mRNA expression of Bax, Bcl-2, Caspase-3, silent information regulator 1, and histone deacetylase 4 in cells was detected by RT-qPCR. RESULTS AND CONCLUSION: (1) Under an optical microscope, cells in the control group showed good growth, forming a dense network with interconnected synapses; cell growth was inhibited in the high glucose and glycemic variability groups, with reduced synaptic connections between cells. The apoptosis rate in the high glucose group was higher than that in the control and glycemic variability groups (P < 0.05), and the apoptosis rate in the glycemic variability group was higher than that in the control group (P < 0.05). (2) On days 3, 4, and 5 of culture, cell viability in the high glucose group was lower than that in the control and glycemic variability groups (P < 0.05), and cell viability in the glycemic variability group was lower than that in the control group (P < 0.05). (3) After 3 and 5 days of culture, reactive oxygen species levels in the high glucose group were higher than those in the control and glycemic variability groups (P < 0.05), reactive oxygen species levels in the glycemic variability group were higher than those in the control group (P < 0.05), and histone deacetylase content in the cell supernatant of the high glucose and glycemic variability groups was higher than that in the control group (P < 0.05). (4) After 3 and 5 days of culture, the protein and mRNA expression of histone deacetylase 4, Bax, and Caspase-3 in the high glucose and glycemic variability groups were higher than those in the control group (P < 0.05), while the protein and mRNA expression of silent information regulator 1 and Bcl-2 were lower than those in the control group (P < 0.05), and Cleaved Caspase-3 protein expression was higher than that in the control group (P < 0.05). Overall, these findings indicate that glycemic variability may induce HT-22 cell apoptosis by upregulating histone deacetylase 4 expression and downregulating silent information regulator 1 expression. Figures and Tables | References | Related Articles | Metrics

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Matrine promotes macrophage polarization to repair myocardial tissue injury in rats Zhao Yongjian, Ge Yunxiao, Yin Yunfei, Jiang Tingbo 2026, 30 (25):  6575-6583.  doi: 10.12307/2026.410 Abstract ( 20 )   PDF (6956KB) ( 7 )   Save BACKGROUND: Matrine exerts therapeutic effects on pneumonia, sepsis, and hepatitis B because of its significant anti-inflammatory and anti-tumor properties. However, its role and mechanisms in macrophage-mediated inflammation post myocardial infarction remain poorly understood. OBJECTIVE: To investigate the effects of matrine on inflammation and myocardial tissue repair following myocardial infarction, and to clarify its potential molecular mechanism. METHODS: (1) In vivo experiment: 32 Sprague-Dawley rats were randomly divided into sham operation group, myocardial infarction group, low-dose matrine [200 mg/(kg·d)] group, and high-dose matrine [300 mg/(kg·d)) group, with 8 rats in each group. Myocardial infarction model was established in rats. Matrine was continuously gavaged for 3 days after surgery. On day 4, echocardiography and serum inflammatory cytokine levels were detected, and heart tissues were obtained for hematoxylin-eosin staining and Masson staining to evaluate myocardial injury severity. (2) In vitro experiment: Mouse bone marrow-derived macrophages were isolated and treated with 10 or 20 μmol/L matrine after lipopolysaccharide was given to establish an inflammatory model. The expression levels of M1/M2 macrophage polarization markers (inducible nitric oxide synthase, CD86, arginase-1, CD206) and their proportional changes were analyzed by western blot, RT-qPCR, and flow cytometry. Phosphorylated levels of Janus kinase 2, signal transducer and activator of transcription 3 were assessed by western blot. Additionally, H9C2 cells were subjected to hypoxic injury to evaluate the effect of matrine on cellular reactive oxygen species levels. RESULTS AND CONCLUSION: (1) In vivo experiment: matrine intervention significantly improved cardiac function in myocardial infarction rats. Compared with the myocardial infarction group, both low- and high-dose matrine treatments significantly increased left ventricular ejection fraction and left ventricular fractional shortening in rats. The high-dose group demonstrated more pronounced improvements than the low-dose group. In addition, matrine significantly inhibited the increase of peripheral inflammatory factors (interleukin 1β and interleukin 6) after myocardial infarction. Histopathological analysis showed that matrine effectively reduces myocardial inflammatory cell infiltration, tissue edema and necrosis. (2) In vitro experiment: RT-qPCR and western blot results showed that matrine significantly downregulated the expression of M1 macrophage markers (inducible nitric oxide synthase and CD86), while upregulated the expression of M2 markers (arginase-1 and CD206). Flow cytometry indicated decreased proportion of CD86-positive cells, and significantly increased proportion of CD206-positive cells. In addition, matrine significantly reduced the intracellular reactive oxygen species levels. (3) Signaling pathway research: Western blot analysis revealed that matrine significantly inhibited the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3, thereby blocking pro-inflammatory signaling pathways and promoting macrophage phenotype switching, ultimately achieving anti-inflammatory effects. These results indicate that matrine dose-dependently promotes macrophage polarization toward the M2 phenotype by inhibiting the Janus kinase 2 and signal transducer and activator of transcription 3 signaling pathway, thereby attenuating post-myocardial infarction inflammatory responses and exerting cardiomyocyte-protective effects. Figures and Tables | References | Related Articles | Metrics

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Functional near-infrared spectroscopy analysis of prefrontal cortex hemodynamics during dual tasks under cognitive loads Guo Zhen, Li Shurui, Zheng Weiwei, Li Ruofei, Li Qingwen 2026, 30 (25):  6584-6591.  doi: 10.12307/2026.478 Abstract ( 13 )   PDF (1977KB) ( 5 )   Save BACKGROUND: In daily life, individuals often operate in a dual-task mode that requires simultaneous execution of motor and cognitive functions. This situation necessitates the coordination of both motor and cognitive functions, placing higher demands on brain workload. Theoretically, the difficulty in cognitive tasks can differentially impact dual-task performance. However, the mechanisms underlying changes in prefrontal cortex hemodynamic responses during motor-cognitive dual tasks under varying cognitive loads remain unclear. Elucidating the hemodynamic responses of the prefrontal cortex under different cognitive loads is highly important for optimizing motor-cognitive training intervention strategies and enhancing training effectiveness and safety. OBJECTIVE: To observe the effects of dual tasks combining narrow-base walking with logical subtraction under different cognitive loads on prefrontal cortex hemodynamics using a portable functional near-infrared spectroscopy device. METHODS: Thirty college students were recruited to complete three task conditions in random order: narrow-base walking (single task), narrow-base walking with serial-3 subtraction (dual task), and narrow-base walking with serial-7 subtraction (dual task). Changes in oxygenated hemoglobin in the prefrontal cortex, subjective cognitive load levels, and dual-task cost were observed. Spatiotemporal gait parameters were simultaneously recorded for behavioral analysis. After testing data normality with the Shapiro-Wilk test, Friedman test and Wilcoxon test were used to analyze differences in prefrontal cortex activation. Repeated measures analysis of variance was employed to compare cognitive load and gait performance. Pearson correlation analysis was conducted to evaluate the relationship between prefrontal cortex activation and cognitive loads. RESULTS AND CONCLUSION: (1) Compared with narrow-base walking alone, both dual-task conditions (serial-3 and serial-7) significantly increased multi-channel activation in the prefrontal cortex (P < 0.05). However, activation in the dorsolateral prefrontal cortex was higher under the serial-3 condition than the serial-7 condition (P < 0.05). (2) As task difficulty increased, accuracy rates significantly decreased (P < 0.01), and gait parameters such as step length, stance phase, and swing phase further declined (P < 0.05-0.01), while dual-task cost increased (P < 0.01). (3) Significantly activated channels in the prefrontal cortex were positively correlated with mental demand, temporal demand, effort, frustration, and overall task load, and negatively correlated with task performance. Significant correlations were observed between activated channels in the prefrontal cortex and mental demand, temporal demand, effort, frustration, and overall task load, while negative correlations were found with task performance. To conclude, these findings suggest that selecting a moderate cognitive load during dual-task interventions facilitates adequate activation of prefrontal cortical resources without overloading, thereby achieving a better balance between cognitive and motor tasks. The results reveal the interaction mechanism between motor and cognitive functions in dual tasks, providing scientific support for optimizing the effectiveness and safety of motor-cognitive dual-task training. Figures and Tables | References | Related Articles | Metrics

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Gut microbiota and short-chain fatty acids: mechanisms of aerobic exercise regulation in type 2 diabetes Feng Shuo, Cao Xuan, Guo Xieleiya, Wang Jingfeng, Li Xiaolin 2026, 30 (25):  6592-6602.  doi: 10.12307/2026.261 Abstract ( 18 )   PDF (13882KB) ( 14 )   Save BACKGROUND: Recent studies have shown that exercise modulates gut microbiota and glucose metabolism; however, the mechanism linking exercise to gut microbiota and short-chain fatty acid production in type 2 diabetes remains unclear. OBJECTIVE: To investigate the mechanism by which exercise modulates gut microbiota composition and short-chain fatty acid metabolism to treat type 2 diabetes. METHODS: Twenty male Sprague-Dawley rats were randomly divided into a control group (n=6) and a model group (n=14). The rats in the model group were fed a high-sugar, high-fat diet for 8 weeks to induce insulin resistance. Following 12 hours of fasting (water allowed), rats received a tail vein injection of 1% streptozotocin solution (35 mg/kg) to damage pancreatic β-cells and elevate blood glucose, establishing type 2 diabetes models. Following successful modeling, feeding protocols remained unchanged. Twelve type 2 diabetes rats were divided into a model group (n=6) and an exercise group (n=6), and the exercise group were subjected to 12 weeks of aerobic exercise. Following the final aerobic exercise, blood samples were collected for glycemic parameter analysis, and fresh fecal samples were obtained for short-chain fatty acid determination using gas chromatography-mass spectrometry. Total microbial DNA was extracted from fresh feces for PCR amplification and purification, followed by high-throughput sequencing using the NovaSeq platform to obtain raw sequence data. Species annotation was performed using the SILVA database. Differential microbiota were screened based on effect sizes from linear discriminant analysis. MetaCyc functional pathways were used to explore associations between exercise intervention and pathways related to glucose and lipid metabolism. Correlations between key microbiota and biochemical indicators were analyzed using heatmaps and visual network diagrams. RESULTS AND CONCLUSION: (1) After 12 weeks of aerobic exercise, glucose and lipid metabolism disorders were significantly improved, inflammatory response was significantly reduced, insulin sensitivity was significantly reduced, and fasting blood glucose significantly decreased rats in the exercise group (P < 0.01). (2) α-Diversity analysis showed that gut microbiota richness (Chao index), coverage (Coverage index), diversity (Shannon index), and evenness (Simpson index) were significantly enhanced in the exercise group compared with the model group (P < 0.05). (3) Abundance charts, correlation heatmaps, and network visualization analyses showed that the abundance of short-chain fatty acids produced in the Firmicutes was significantly increased in the exercise group, such as Colidextribacter and Intestinimonas, which showed strong positive correlations with the levels of short-chain fatty acids, such as hexanoic acid and valeric acid, while simultaneously suppressing the production of pathogenic bacteria within the phylum Proteobacteria, such as Klebsiella and Turicibacter, which showed negative correlations with short-chain fatty acid levels. Lactobacillus promotes short-chain fatty acid production (e.g., butyric acid) and negatively correlates with glycolipid metabolism, inflammatory markers, fasting blood glucose, and interleukin-6 (P < 0.05). (4) Metabolic function predictions based on KEGG and MetaCyc reveal that aerobic exercise reshapes energy homeostasis by bidirectionally regulating microbial metabolic pathways. Exercise significantly downregulates pathways associated with excessive glycogenolysis and lipolysis as well as pro-inflammatory metabolism, while simultaneously upregulating key short-chain fatty acid synthesis pathways and glycolytic homeostasis pathways. This functional remodeling highly correlates with the restoration of short-chain fatty acid-producing Firmicutes abundance and the suppression of pathogenic Proteobacteria (P < 0.05). (5) These findings suggest a closed-loop regulation where the dynamic balance of gut microbial metabolic pathways interacts with improved host glucose and lipid metabolism and reduced inflammatory markers, indicating that gut microbiota, short-chain fatty acid synthesis, and metabolic function remodeling constitute the core mechanisms by which exercise ameliorates the pathological progression of diabetes. Figures and Tables | References | Related Articles | Metrics

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Effects of blood flow restriction training and aerobic exercise on energy expenditure in young men Liu Meng, Hou Shilun 2026, 30 (25):  6603-6609.  doi: 10.12307/2026.486 Abstract ( 16 )   PDF (1365KB) ( 7 )   Save BACKGROUND: In recent years, high-intensity interval exercise has been widely used and gained attention due to its short duration. However, its safety has been seriously questioned because of its high intensity and the controversial effects on the heart. Therefore, exploring time-efficient, intensity-controllable exercise interventions with good compliance has become a research hotspot in the field of exercise science. OBJECTIVE: To investigate the effects of blood flow restriction combined with aerobic exercise on energy expenditure. METHODS: Fifteen male college students were recruited. A repeated-measures crossover design was used to design two exercise protocols: low-intensity aerobic exercise (non-blood flow restriction group) and blood flow restriction training combined with low-intensity aerobic exercise (blood flow restriction group). Both protocols were performed at 40% maximal oxygen uptake, with 10 minutes of running per session, 1 minute rest between sessions, for a total of five sessions and an exercise duration of 54 minutes. In the blood flow restriction group, a cuff was placed at the most proximal end of both lower limbs and pressurized to 50% of the arterial occlusion pressure before exercise, and the pressure was released during each exercise interval. The interval between the two exercise protocols was at least 72 hours. Blood lactate, energy expenditure during exercise, excess post-exercise oxygen consumption, rating of perceived exertion, heart rate, and blood pressure were measured. RESULTS AND CONCLUSION: (1) Total energy expenditure was significantly higher in the blood flow restriction group than in the non-blood flow restriction group (P < 0.05). (2) There was no significant difference in the energy supply ratios of the three major energy systems (aerobic, anaerobic-lactate, and anaerobic-phosphagen) between the non-blood flow restriction group and the blood flow restriction group (P > 0.05). (3) The total excess post-exercise oxygen consumption within 40 minutes of the exercise recovery period was significantly higher in the blood flow restriction group than in the non-blood flow restriction group (P < 0.05). Heart rate at 1 minute of the recovery period was significantly higher in the blood flow restriction group than in the non-blood flow restriction group (P < 0.05), while there were no significant differences in rating of perceived exertion, heart rate, or blood pressure between the two groups at other time points. To conclude, these findings indicate that blood flow restriction training combined with low-intensity aerobic exercise can increase energy expenditure and excess post-exercise oxygen consumption without additionally increasing the rating of perceived exertion, providing an additional training option for individuals seeking to improve their physical activity levels. However, attention should be paid to the increase in heart rate during the recovery period. Figures and Tables | References | Related Articles | Metrics

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Role of bone–blood axis in bone mass regulation and hematopoietic function maintenance Hong Linling, Zhang Kunpeng, Zheng Liming, Ye Baodong, Liu Jingjing, 2026, 30 (25):  6610-6620.  doi: 10.12307/2026.295 Abstract ( 11 )   PDF (1995KB) ( 6 )   Save BACKGROUND: The bone marrow serves not only as a primary hematopoietic organ but also as an essential component of bone tissue. The bone marrow microenvironment is a critical niche for maintaining hematopoietic stem cell function, while the hematopoietic process, in turn, regulates bone mass homeostasis. The precise synergistic effect between the skeletal and hematopoietic systems maintains the health of both systems, but a systematic summary of the interactions between these two systems is still lacking. OBJECTIVE: To systematically review the research progress on the interaction between the skeletal and hematopoietic systems, aiming to provide a reference for their mutual regulation, and to explore potential therapeutic targets for hematological diseases such as anemia and leukemia, and skeletal diseases such as osteoporosis and osteoarthritis through analysis of previous literature. METHODS: We searched the CNKI, WanFang, and PubMed databases for literature related to the article's topic from January 2000 to July 2025, using search terms such as "bone mass regulation, hematopoietic function, bone marrow microenvironment, bone and blood axis." We selected works, research papers, and review articles, ultimately including 115 articles for analysis. RESULTS AND CONCLUSION: (1) This study systematically expounds the bidirectional regulatory network of the "bone-blood axis" in the bone marrow microenvironment and its core mechanisms. (2) The research results show that the bone marrow microenvironment, as a dynamic system composed of various cellular and non-cellular components, not only precisely regulates the quiescence, self-renewal and differentiation of hematopoietic stem cells through core signaling pathways such as Wnt/β-catenin, Notch, nuclear factor κB receptor activator/nuclear factor κB receptor activator ligand/osteoplastin and Hippo-YAP, but also receives reverse regulation from the hematopoietic system. (3) This bidirectional dialogue also dominates the bone remodeling process, in which immune cells (such as macrophages and T lymphocytes) secrete specific factors and become the key bridges connecting the skeletal system and the hematopoietic system. (4) The imbalance of this dialogue network is an important pathological basis for the occurrence of cross-system diseases such as osteoporosis, myelofibrosis and leukemia. (5) This article uses the "bone-blood axis" as a framework to understand the bone marrow microenvironment, providing a new perspective for revealing the co-pathogenesis of hematological and skeletal diseases; targeting the key signaling nodes of this axis or using coordinated intervention strategies (such as denosumab and romiplostim), is expected to open up new paths for the integrated treatment of cross-system diseases in the future. Figures and Tables | References | Related Articles | Metrics

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A new approach to intervene in Alzheimer's disease through regulating the silencing information regulator 1 signaling pathway with traditional Chinese medicine Zhao Fangfang, Guo Yanke, Wang Xueke, Pang Botong, Zhu Yanqiang, Qin Yang, Cui Yinglin 2026, 30 (25):  6621-6631.  doi: 10.12307/2026.274 Abstract ( 19 )   PDF (1766KB) ( 5 )   Save BACKGROUND: Silent information regulator 1, as a deacetylase, can regulate the transcriptional activity of various proteins and many Alzheimer’s disease related pathological processes after activation, including regulating energy metabolism, oxidative stress, neuroinflammation, autophagy, and cell apoptosis. It is closely related to the occurrence, development, and prognosis of Alzheimer’s disease. In recent years, a large number of studies have found that the active ingredients and formulas of traditional Chinese medicine monomers can delay the development of Alzheimer's disease by activating the silent information regulator 1 signaling pathway, reducing cell apoptosis, protecting neurons, and inhibiting the formation of amyloid plaque. OBJECTIVE: To explore the relationship between silent information regulator 1 and Alzheimer’s disease, as well as the action mechanism of traditional Chinese medicine in regulating the silent information regulator 1 signaling pathway for the treatment of Alzheimer’s disease. METHODS: The CNKI, WanFang, VIP, SinoMed, and PubMed databases were searched using keywords: “Alzheimer's disease, dementia, SIRT1, inflammation, oxidative stress, inflammatory factors, signaling pathways, TCM monomers, compounds” in Chinese and English from January 2015 to March 2025 to search the articles addressing silent information regulator 1 and the regulatory mechanisms of traditional Chinese medicine. The literature that is not highly relevant to the study, repetitive, or outdated, were excluded. A total of 4 921 relevant articles were retrieved, and 154 articles were ultimately included for review. RESULTS AND CONCLUSION: (1) Numerous experimental studies have confirmed that silent information regulator 1 plays an important role in Alzheimer's disease. (2) Traditional Chinese medicine can regulate the silent information regulator 1 signaling pathway through various means, such as sodium ferulate can improve the learning and memory abilities of Alzheimer's disease rats by enhancing the expression of silent information regulator 1 in the prefrontal cortex of Alzheimer's disease, thereby ameliorating neuronal damage caused by ischemia and hypoxia. Oyster peptides can enhance reactive oxygen species, reduce oxidative damage in hippocampal tissue, alleviate neuroinflammation, enhance synaptic function, reduce neuronal damage and death, exert neuroprotective effects, and improve cognitive dysfunction. Figures and Tables | References | Related Articles | Metrics

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Action mechanisms of Bushen Qiangjin capsule in regulating inflammatory signaling pathways and improving knee osteoarthritis He Wenyang, Chen Weijian, Ran Qingzhi, Huang Yidie, Lin Xiaodong, Xu Xuemeng, Guo Meirong, Liu Wengang 2026, 30 (25):  6632-6642.  doi: 10.12307/2026.287 Abstract ( 19 )   PDF (32390KB) ( 7 )   Save BACKGROUND: Animal experiments have demonstrated that Bushen Qiangjin capsule can significantly improve subchondral bone metabolism and abnormal bone remodeling, and delay the progression of knee osteoarthritis, providing experimental evidence for elucidating the mechanism of action of this drug in treating knee osteoarthritis. OBJECTIVE: To systematically explore the mechanism of action of Bushen Qiangjin capsule in regulating inflammatory signaling pathways to improve knee osteoarthritis using network pharmacology, Mendelian randomization based on pooled data, two-sample Mendelian randomization, molecular docking, and cell experiments. METHODS: (1) The effective components, core targets, and signaling pathways of Bushen Qiangjin capsule in treating knee osteoarthritis were obtained using network pharmacology tools. Potential targets were imported into the STRING platform to construct a protein interaction network for further screening of core targets. Mendelian randomization analysis based on pooled data was conducted to assess the causal relationship between core targets and the risk of knee osteoarthritis. Two-sample Mendelian randomization was used to analyze the causal relationship between mitogen-activated protein kinase 8 and knee osteoarthritis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on potential targets of Bushen Qiangjin capsule in intervening in knee osteoarthritis. Molecular docking was used to further clarify the interaction between the key active ingredients of Bushen Qiangjin capsule and its core target protein. (2) Five Sprague-Dawley rats were administered Bushen Qiangjin capsule at a dose of 0.243 g/kg per day via gavage for 7 consecutive days. Venous blood was collected after the last administration, and serum containing the drug was separated. Chondrocytes from the rat knee were cultured in three groups: a blank group received no treatment; a model group was treated with interleukin-1β for 24 hours to establish an osteoarthritis cell model; and a serum-containing group was treated with interleukin-1β for 24 hours followed by treatment with 10% drug-containing serum (volume fraction) for 24 hours. After treatment, chondrocyte morphology was observed by alicin blue and toluidine blue staining. The mRNA and protein expression of mitogen-activated protein kinase 8 and type II collagen were detected by RT-qPCR and western blot assay. RESULTS AND CONCLUSION: (1) A total of 85 active ingredients related to Bushen Qiangjin capsule were obtained, among which kaempferol and ferulic acid were key components. Core targets included serine/threonine protein kinase 1 and phosphatidylinositol 3-kinase catalytic subunit α. Mendelian randomization and two-sample Mendelian randomization analyses based on the aggregated data indicated a direct causal relationship between mitogen-activated protein kinase 8 and knee osteoarthritis, and this relationship was positive. Gene Ontology enrichment results mainly involved biological processes such as phosphorylation, response to heterobiotic stimuli, and negative regulation of apoptosis. The Kyoto Encyclopedia of Genes and Genomes pathways mainly included signaling pathways such as phosphatidylinositol 3-kinase-serine/threonine protein kinase, tumor necrosis factor α, Toll-like receptor 4, hypoxia-inducible factor 1, and mechanosensory-related axes. Molecular docking results showed that kaempferol and ferulic acid exhibited good binding activity to core targets such as serine/threonine protein kinase 1, phosphatidylinositol 3-kinase catalytic subunit α, tyrosine kinase C, signal transduction and transcription activator 3, and tumor protein p53. (2) Alcian blue and toluidine blue staining showed that Bushen Qiangjin capsule promoted the synthesis of extracellular matrix in an osteoarthritis cell model. RT-qPCR and western blot analysis showed that, compared with the model group, the mRNA and protein expression levels of type II collagen were increased in the serum-containing group (P < 0.05), while the mRNA and protein expression levels of mitogen-activated protein kinase 8 were decreased (P < 0.05). (3) The results indicate that Bushen Qiangjin capsule may improve knee osteoarthritis-related damage by synergistically regulating inflammatory responses and extracellular matrix homeostasis through a multi-component, multi-target, and multi-pathway approach. Figures and Tables | References | Related Articles | Metrics

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Visualization analysis on research literature about animal models for osteonecrosis of the femoral head Bai Ruokun, Mo Jian, Han Jie, Li Kunjian, Nie Xiayu, Chen Shuai 2026, 30 (25):  6643-6653.  doi: 10.12307/2026.291 Abstract ( 15 )   PDF (4945KB) ( 6 )   Save BACKGROUND: Osteonecrosis of the femoral head is a refractory disorder characterized by osteocyte apoptosis and structural collapse of the femoral head. Its pathogenesis is closely associated with vascular injury, dysregulated bone metabolism, and aberrant mechanical stress. In recent years, animal models have served as indispensable tools for simulating pathological processes, playing an irreplaceable role in elucidating molecular mechanisms of osteonecrosis of the femoral head and evaluating novel interventions. Nevertheless, the standardization of model development and their clinical translational value require systematic investigation. OBJECTIVE: To analyze the research landscape in the field of osteonecrosis of the femoral head using bibliometric approaches, with an emphasis on evaluating the application characteristics, limitations, and future optimization directions of animal models in study design, providing a reference for advancing mechanistic understanding and therapeutic development. METHODS: Literature published between January 2015 and March 2025 was retrieved from the Web of Science Core Collection (SCI-Expanded) using the search strategy: TS=(osteonecrosis of the femoral head) AND TS=(mouse OR mice OR rat OR rabbit OR dog OR swine OR pig OR sheep OR monkey OR “laboratory animal” OR “experiment animal”). Simultaneously, Chinese literature was screened from CNKI and WanFang databases (January 2015–March 2025) with the query: SU=(osteonecrosis of the femoral head) AND SU=(mouse OR mice OR rat OR rabbit OR dog OR swine OR pig OR sheep OR monkey OR “laboratory animal” OR “experiment animal”). CiteSpace 6.3.R1 software was employed to visualize publication countries, institutions, authors, keywords, and co-cited references. Research trends were synthesized by integrating animal model classifications and application features. RESULTS AND CONCLUSION: (1) Among English publications, China contributed over 80% of studies (n=458). Research hotspots focused on steroid-induced necrosis mechanisms (e.g., oxidative stress-autophagy axis), stem cell/tissue engineering therapies, and traditional Chinese medicine interventions. Analysis revealed that osteonecrosis of the femoral head animal model research exhibits a “high output–weak collaboration” pattern. (2) In Chinese literature, traditional Chinese medicine-related institutions dominated publications, with traditional Chinese medicine interventions and steroid-induced osteonecrosis of the femoral head representing major research foci. (3) Future efforts should prioritize cross-species validation platforms, multi-omics integration, and synergistic development strategies for Chinese and Western medicines to accelerate clinical translation. Figures and Tables | References | Related Articles | Metrics

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Druggable gene and single cell analyses reveal potential therapeutic targets for osteoporosis Li Yiwei, Luo Zongming, Rong Yifa, Jiang Kai, Zhang Jiahao, Lu Bowen, Li Gang 2026, 30 (25):  6654-6660.  doi: 10.12307/2026.383 Abstract ( 12 )   PDF (2041KB) ( 4 )   Save BACKGROUND: Genetic factors play an important role in the pathophysiology of osteoporosis, and Mendelian randomization can be used to infer causal associations between specific genes and diseases using eQTLs. OBJECTIVE: To identify potential therapeutic targets for osteoporosis based on druggable genes-related Mendelian randomization and colocalization analysis, to explore the potential biological mechanisms in the treatment of osteoporosis using bioinformatics analysis, and to predict the binding activity of drug targets using drug enrichment analysis and molecular docking. METHODS: (1) Data sources: Druggable genes were sourced from the DGIdb database (a public database constructed by the University of Washington School of Medicine, widely used for drug target discovery) and information provided in the literature. Expression quantitative trait locus (eQTL) data for druggable genes were obtained from eQTLGen (a large-scale blood eQTL database jointly constructed by multiple international research institutions, including the University of Groningen in the Netherlands). The genome-wide association study data for osteoporosis were obtained from FinnGen R12 (a large-scale genomic database led by the University of Helsinki in Finland), including 10 461 osteoporosis cases and 473 264 controls. GSE230665 chip dataset and GSE169396 single-cell dataset were obtained from the GEO database. (2) Methods: Genes closely associated with osteoporosis were screened. Gene expression specific to osteoporosis was evaluated using array. Single-cell analysis was used to further examine the regulatory role of these genes in cell communication. Additionally, enrichment analysis was performed to elucidate biological functions, and a protein-protein interaction network was constructed to analyze potential associations. Drug enrichment and molecular docking were used to predict and simulate the binding of small molecule drugs with targets. RESULTS AND CONCLUSION: This study identified 37 druggable genes associated with osteoporosis, among which Troponin C2 and CXC chemokine receptor 6 have protective roles in osteoporosis and share causal genetic variations with the disease. Array data analysis showed that CXC chemokine receptor 6 expression was significantly reduced in osteoporosis compared with the normal group, suggesting its diminished protective role in osteoporosis. Single cell analysis further revealed that CXC chemokine receptor 6is predominantly expressed on T cells, and CXC chemokine receptor 6 positive T cells exhibit stronger cell communication abilities. Drug enrichment found that NSC95397 can target and bind CXC chemokine receptor 6, and molecular docking showed good binding activity with CXC chemokine receptor 6. These findings not only provide clues for the development of novel osteoporosis drugs but also promote the translation and application of research outcomes. Figures and Tables | References | Related Articles | Metrics

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Neutrophils and the repair of hard-to-heal wounds Liu Yufei, Chang Jinxia, Mi Baolai, Yuan Liang, Gu Hancheng, Cao Jianchun 2026, 30 (25):  6661-6668.  doi: 10.12307/2026.834 Abstract ( 12 )   PDF (16812KB) ( 14 )   Save BACKGROUND: Dysfunction of neutrophils in the microenvironment of refractory wounds and their abnormal interactions with other immune cells and repair cells have become a central research focus for understanding the pathophysiology of chronic wounds and developing novel intervention strategies. OBJECTIVE: To investigate the current research status, hotspots, frontiers, and development trends regarding neutrophils in the field of hard-to-heal wound repair. METHODS: Relevant literature regarding neutrophils in the repair of hard-to-heal wounds published between 2004 and 2024 was retrieved from the Web of Science Core Collection database. Bibliometric visualization analysis methods were employed for analysis and visualization, revealing the research landscape, major hotspots, and frontier trends from dimensions including publication volume, countries/regions, institutions, authors, journals, references, and keywords. RESULTS AND CONCLUSION: A total of 1 062 relevant articles concerning neutrophils in hard-to-heal wound repair were included. The annual publication output in this field showed a significant growth trend, accelerating markedly after 2014. Publications exceeded 100 in 2023, indicating increasing academic attention. The United States led globally with 378 publications, boasting an extensive international collaboration network. China ranked second with 189 publications, demonstrating strong research vitality; however, there remains potential for enhancing international collaboration and citations per paper. Shanghai Jiao Tong University (China) was the most prolific institution, while the University of Illinois and Harvard University (USA) emerged as central hubs for citation frequency. Journal analysis identified Wound Repair and Regeneration as the core journal leading in both publication volume and citation count. Research hotspots focus on inflammation, angiogenesis, and diabetic foot ulcers, among others. Keyword clustering timeline and burst analyses revealed that neutrophil extracellular trap formation and neutrophil-macrophage interactions represent frontier research trends. These results indicate that a clear developmental trajectory has emerged in this field, spanning from clinical problems to molecular mechanisms, and further towards immunomodulatory intervention strategies. In the future, precise regulation of neutrophil functions holds promise for opening new avenues in the treatment of hard-to-heal wounds. Figures and Tables | References | Related Articles | Metrics

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Causal relationship between immune cell-mediated circulating inflammatory proteins and rheumatoid arthritis Wang Chun, Gan Lizhen, Ren He, Fang Yi, Gao Zishan, Wu Yunchuan 2026, 30 (25):  6669-6679.  doi: 10.12307/2026.267 Abstract ( 17 )   PDF (6498KB) ( 9 )   Save BACKGROUND: Studies have shown that circulating inflammatory proteins and immune cells are associated with rheumatoid arthritis, but the causal relationship is unclear. OBJECTIVE: To explore the causal relationships between circulating inflammatory proteins and rheumatoid arthritis mediated by immune cells. METHODS: We downloaded data on circulating inflammatory proteins and immune cell phenotypes from the GWAS Catalog database (a publicly accessible database jointly established and maintained by the National Human Genome Research Institute and the European Bioinformatics Institute), and genome-wide association study data for rheumatoid arthritis from the FinnGen database (a genomics project resulting from collaboration between Finnish research institutions, biobanks, and international industry partners, also publicly accessible). A two-step Mendelian randomization analysis was then conducted. In the first step, inverse variance weighted method was used to evaluate the causal effects of 91 circulating inflammatory proteins and 731 immune cells on rheumatoid arthritis risk. MR-Egger, weighted median, weighted mode, simple mode, and sensitivity analyses were performed to ensure robustness and assess pleiotropy. The second step evaluated the mediating effects of identified immune cells on the relationship between circulating inflammatory proteins and rheumatoid arthritis. RESULTS AND CONCLUSION: (1) Inverse variance weighted analysis showed that four circulating inflammatory proteins were significantly correlated with the risk of rheumatoid arthritis, with one circulating inflammatory protein being a risk factor for rheumatoid arthritis and three circulating inflammatory proteins being protective factors for rheumatoid arthritis. Forty-six kinds of immune cells were significantly associated with rheumatoid arthritis, comprising 20 risk factors and 26 protective factors. Reverse Mendelian randomization analysis found no causal associations between rheumatoid arthritis and four identified circulating inflammatory proteins. Sensitivity analyses revealed no significant heterogeneity or horizontal pleiotropy. Further Mediation analysis showed that CD19 on IgD- CD38br partially mediated the causal effect of interleukin-18 on rheumatoid arthritis (β=0.064, odds ratio=1.066, P=0.044), with a mediation effect of 0.004, accounting for 5.7% of the total effect, and a direct effect of 0.060. (2) The study findings reveal that circulating inflammatory proteins and immune cells have causal associations with rheumatoid arthritis, and demonstrate that CD19 on IgD- CD38br partially mediates the causal effect of interleukin-18 on rheumatoid arthritis. With the rich accumulation of data in international multi-omics research platforms and trans-ethnic cohorts, China can reference their multi-dimensional data integration frameworks to construct a dedicated database integrating epigenomics, proteomics, and metabolomics for the Chinese population, revealing molecular regulatory networks underlying complex diseases and aiding in disease subtyping and early diagnostic biomarker development. Learning from transnational collaborative research mechanisms, establishing multi-ethnic and multi-regional natural population cohorts in China will systematically dissect the impact of gene-environment interactions on health, providing a scientific basis for localized disease prevention strategies. Figures and Tables | References | Related Articles | Metrics

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Bibliometric analysis of trends and hotspots in immune cells for fibrotic diseases Zhang Shuangzhen, Pan Ling, Liu Rui 2026, 30 (25):  6680-6690.  doi: 10.12307/2026.441 Abstract ( 13 )   PDF (16127KB) ( 9 )   Save BACKGROUND: Research on multi-organ fibrotic diseases has gained increasing prominence in recent years. Immune cells play a crucial regulatory role in the pathogenesis of fibrotic diseases across various organs; however, a comprehensive bibliometric analysis in this specific research field is currently lacking. OBJECTIVE: To systematically analyze the current research status, hotspots, and emerging trends in the field of immune cells and fibrotic diseases using bibliometric methods. METHODS: Publications on immune cells and fibrotic diseases of the liver, lungs, kidneys, and heart were collected from the Web of Science Core Collection database spanning January 1, 2000 to December 31, 2024. Bibliometric and visual knowledge mapping analyses were performed on the extracted data using VOSviewer, CiteSpace, and the R package "bibliometrix". RESULTS AND CONCLUSION: A total of 1 777 relevant articles were identified. These publications were contributed by 11 347 authors from 2 239 institutions across 73 countries and were published in 637 academic journals. From January 1, 2000 to December 31, 2024, the annual publication output demonstrated a consistent upward trend. China, the United States, and Germany were the leading contributing countries. Zhejiang University and Huazhong University of Science and Technology (China) were the most productive institutions, while Uniklinik RWTH Aachen (Germany) received the highest total citation count. The most prolific journal was Frontiers in Immunology. Frank Tacke and Christian Trautwein were the most published authors. The core keywords included liver fibrosis, pulmonary fibrosis, macrophages, expression, and activation. Overall, bibliometric analysis reveals a paradigm shift in this field, transitioning from a focus on single organs to a shared understanding of immune mechanisms. Research on fibrotic diseases has evolved from initial basic studies on liver fibrosis to the targeted molecular and cellular regulation of fibrosis in multiple organs, including the heart, lungs, and kidneys. Figures and Tables | References | Related Articles | Metrics

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Diabetes mellitus and ferroptosis: a visual analysis of related research literature Chen Xianxian, Xu Chengfeng, Huang Wenyi, Yang Chenfan, Su Tongshan, Li Yu, Yan Yu, Li Chun 2026, 30 (25):  6691-6700.  doi: 10.12307/2026.402 Abstract ( 14 )   PDF (9799KB) ( 9 )   Save ACKGROUND: Oxidative stress induced by chronic hyperglycemia and impaired antioxidant systems are one of the core mechanisms underlying the onset and progression of diabetes mellitus. Ferroptosis, a new type of programmed cell death caused by iron-dependent lipid peroxidation, has received considerable academic interest due to its association with diabetes. OBJECTIVE: To reveal the current status and trends of ferroptosis-related research in the field of diabetes mellitus using bibliometric methods, aiming to offer academic resources to further develop this research area. METHODS: Based on the Web of Science Core Collection database, with a time span set from January 1, 2015 to January 1, 2025, 797 articles related to ferroptosis in the field of diabetes mellitus were retrieved. A visual analysis was conducted on 758 high-quality articles obtained after removing duplicates using the knowledge mapping software CiteSpace (6.2.R1), including publication volume, country/institutional collaboration, co-citations of high-impact authors/articles, keyword co-occurrence/clustering/emergence, international frontier trends, and visualization of scientific networks. RESULTS AND CONCLUSION: (1) Bibliometric analysis indicates a substantial increase in ferroptosis-related research within the field of diabetes mellitus, with 758 records meeting criteria for systematic analysis. (2) Andreas Linkermann was the most prolific author, while Dixon SJ set an academic influence benchmark with 420 citations. The journal Cell demonstrated the highest co-citation frequency. The dominant keywords included oxidative stress, cell death, and lipid peroxidation, with their clusters primarily concentrated in diabetic nephropathy and cardiomyopathy, glutathione peroxidase 4, and programmed necrosis. (3) The investigation into ferroptosis regulatory networks in applications is growing, establishing itself as a novel approach for targeted therapy research in diabetes mellitus and its complications. Figures and Tables | References | Related Articles | Metrics